Outline

Objective

Mortality of brain edema after ischemic stroke in the MCA territory is as high as 80% under conservative treatment. Therefore, hemicraniectomy is applied as a life-saving invasive therapy. Selection of patients who benefit from hemicraniectomy and determination of the time point when the intervention must be performed is essential for successful implementation. We applied an invasive neuromonitoring including microdialysis, ICP, CPP and tissue oxygen pressure (ptO2) in patients with large MCA infarction. The aim of this study was a) to identify predictors of malignant course, b) to determine the time point of critical deterioration from the course of pathophysiological markers and c) to assess the effect of hemicraniectomy on brain metabolism.

Methods

34 patients with stroke of >50% of the MCA territory in early cerebral CT or MRI scan were included. Probes for microdialysis and measurement of ICP and ptO2 were placed into the ipsilateral frontal lobe (peri-infarct-tissue) using a 3-channel bolt kit. ICP, ptO2 and extracellular concentrations of transmitter, neuromodulator and non-transmitter amino acids (non-TAA) as well as energy-related metabolites like lactate, pyruvate, glycerol and several purine catabolites were measured continuously for five days. According to clinical course and brain swelling in the CT scan, patients were categorized into a malignant group or a benign group. Patients who were hemicraniectomized had signs of local brain swelling such as effacement of the sulci and compression of the lateral ventricle on follow-up CT; they also showed neurological deterioration consisting of a further decrease in consciousness to somnolence and stupor before hemicraniectomy was performed and were therefore assigned to the group with malignant clinical course. Neurological deficit was assessed by the National Institute of Health Stroke Scale (NIHSS), outcome by the modified Rankin Scale (mRS) after 3 months.

Results

17 patients suffered malignant course, of whose 11 patients were treated conservatively and 6 patients underwent hemicraniectomy. The 17 patients with benign course did not develop malignant brain swelling. Significant correlations between clinical outcome and peak values troughout the measurement were observed for the transmitter amino acids glutamate, aspartate, and GABA; for glycerol as an indicator for membrane degradation; for the energy metabolites lactate-pyruvate ratio and hypoxanthine; and for ICP, CPP, and PtO2. Only patients with malignant course showed marked changes in substrate concentrations in the later course of ischemia indicating enlargement of infarction by secondary ischemia: ICP continuously increased and consequently CPP decreased. When CPP fell to <50 to 60 mm Hg, concentrations of excitatory amino acids, GABA, and energy metabolites started to increase. At this point, ptO2 decreased and fell to <10 mm Hg. In contrast to those changes occuring days after stroke onset, the concentrations of non-TAA showed significant differences between the two groups already in the first 12 h of measurement with lower concentrations in patients with malignant course than in patients with benign course. This decrease of non-TAAs may be attributed to a dilution of substances in an expanded extracellular space resulting from vasogenic edema of infarcted tissue. In 3 patients monitoring was started before hemicraniectomy and continued afterwards. The stable values for transmitter amino acids and energy metabolites indicated that the operation was not harmful to the peri-infarct tissue, which remained in a non-ischemic state and its metabolism widely intact.

Conclusions

We conclude that invasive neuronitoring in patients with large MCA infarction a) helps to predict malignant brain edema and thereby to select patients eligible for hemicraniectomy, b) helps to classify the clinical courses by characterizing pathophysiological sequelae of malignant edema formation, particularly growth of infarction by secondary ischemia and c) can be used to evaluate the therapeutic impact of hemicraniectomy by monitoring the effects of the operation on brain metabolism.